
Welcome back! 
So today is going to be our third lecture 
in this course, and we want to talk about 
the, the division between the cell and 
its extracellular environment. 
As I said in the very first lecture, that 
every cell has a membrane around it, and 
that membrane forms a hydrophobic 
barrier, and that prevents ions or any 
charged molecules from moving from the 
extracellular space into the interior of 
the cell. 
So that, that exit and entrance of these 
hydrophilic molecules, so those charged 
molecules, is going to be regulated by 
the cell. 
And so today we want to talk about the 
kinds of proteins that are used to 
regulate the exit and entrance of 
hydrophilic materials from from 
ourselves. 
So the learning objectives then are one, 
we're going to describe the, how solutes, 
these, are moving across the cell 
membranes. 
Two, we want to explain how charge, size 
and their solubility will affect the 
solute movement across the membranes. 
Three, we want to contrast how the 
transporters, pumps and channels work, so 
these are the proteins that are going to 
mediate the movement of, of hydrophilic 
materials, that is charged materials, 
across the membranes. 
And lastly we want to describe how the 
ion channels are gated, that is the 
regulation of movement across these 
channels. 
So the first thing is that you have to 
remember that the cells have a 
hydrophobic barrier and that this barrier 
is a by-layer of lipid. 
So this lipid then, this by-layer of 
lipid allows hydrophobic materials to 
come across but not the charged entities. 
But our physiology the process, the 
physiological processes are controlled by 
a lot of signals that are coming from the 
extracellular space. 
And it has to come in to the cells or 
they have to change the property of the 
cell in some manner and the kinds of 
physiological processes that are 
controlled are one growth, two our 
metabolic processes. 
We have to be able to move fuel across 
the membranes, for instance. 
So glucose has to be able to enter into 
cell. 
And then thirdly, we're going to use some 
of this movement across membranes. 
To signal information from the 
environment back into the body to the 
integration center, which is our brain. 
and then back out to the affectors. 
So in order to be able to govern these 
the nervous system, we have to be able to 
convert chemical information, which is 
coming in from the environment, into an 
ion. 
And this ion then travels the ion flow is 
going to then take the information to the 
brain, where it can recognize the 
information. 
And then the, send out, also by ion flow, 
to the effectors to something like glands 
or to, to the muscle. 
The other reason that we're interested in 
this topic, is, is that, this is really 
the basic of, a basis of many diseases. 
When we have defective, transporters, 
such as in cystic fibrosis. 
Then materials are not positioned 
correctly across the membranes. 
For instance, in cystic fibrosis. 
The chloride is not moving across the 
membrane correctly and because the 
chloride ion is not moving correctly 
water is not moving correctly across 
these membranes. 
Consequently the mucus, which is secreted 
by the lung as a protective barrier 
becomes very, very thick and viscus, and 
then there is a difficulty then for 
transporting gases across this, across 
this mucus layer. 
so that it can, the oxygen then can get 
into the, into the blood. 
The other one is, is that we can have 
defective channels. 
And we'll talk about it what channels are 
in a minute, but in these cases, then 
the, the channels can be allowing calcium 
or sodium or potassium to be moving 
across the membranes. 
In the long QT syndrome of the heart, we 
find that the, that these, some of these 
channel are defective and that then, 
changes the way the heart is able to, to 
have its beat and because the beat is, is 
prolonged then what happens is that the 
heart can go into arrhythmia. 
The other thing, that we should notice, 
is that, these channels, and the pumps 
and the transporters often are the target 
sites for therapy. 
For, for our drug therapies. 
So, for instance, when you have 
hypertension, and somebody has a, a blood 
pressure that's very high. 
they maybe treat it with a diurhetic. 
The diuretic inhibits the ability of a 
sodium transporter to move sodium across 
membranes and therefore water cannot 
follow sodium. 
And what happens then is that the sodium 
and the water are peeled out from the 
body, so we increase the amount of urine 
production from the body. 
By doing so you decrease the volume of 
the ECF, and by decreasing volume of the 
ECF, you decrease blood pressure. 
We also have drugs that can be used to 
treat stomach ulcers. 
So in stomach ulcers you have an erosion 
of the epithelial cells that line the 
stomach and under these conditions the 
acid is the causa-, the causative Agent. 
By blocking the ability to make acid in 
the stomach, then the ulcer can heal. 
And so these are called proton pump 
inhibitors. 
And when we talk about the, the, the 
stomach and its activity. 
The physiological role of the stomach, 
and its ability to make acid in the GI 
tract. 
that is the gastrointestinal tract. 
Then we'll be talking about these proton 
pump inhibitors. 
Alright, so let's look at very simplest 
way of moving materials across the plasma 
membrane and that's what is diagrammed 
here. 
So if we have if you can imagine that, 
that we have a plasma membrane which is, 
which is here and that this plasma 
membrane then again is going to be our 
bilayer of lipids with a hydrophobic 
barrier. 
And we have the ICF is the yellow 
component. 
And outside of that we have our ECF. 
So we have this orange material which is 
sitting in the ECF. 
And the membrane is able to allow this 
material to, to cross the membrane. 
So this, this material is permeable to 
the membrane. 
So the material then can enter into the 
ICF and it will enter by gumming down 
this concentration gradient. 
So it has high concentration of the 
orange material in the ECF, and so the 
dominant movement of the material is 
toward the interior of the cell because 
the cell has very low concentration of 
the material. 
This is by whats called diffusion and 
that this is simply a random movement of 
particles going across this permeable 
membrane. 
Because the plasma membrane is a bilayer 
of lipids any molecule that is soluble in 
hydrophobic materials, that is, is 
soluble in lipids such as urea, can 
easily pass across the plasma membrane. 
So the orange material could be urea. 
So as the urea then enters into the cell, 
we also have a very small flow of the 
urea back towards the, towards the ECF. 
But this is a very small flow, because we 
have a very very high concentration of 
the urea in the ECF and a very low 
concentration in the ICF. 
The flux, which is going to be the random 
movement of this material across the 
surface per unit time is going to be 
determined by the gradient. 
So the net flux is determined by the 
gradient, and we go from a high 
concentration to a low concentration. 
And this is called simple diffusion. 
Now, simple diffusion can also occur 
between two cells. 
For instance, in the cardiac myocyte, we 
have a small junction which is called a 
gap junction, or a nexus, and this 
structure. 
Is a little pore that's between the two 
cells, two adjacent cells. 
If we have a high concentration of 
calcium in the first cardiac myocyte, 
this calcium can diffuse through the, 
through the gap junction to the second 
cell. 
Which is shown here, and again the 
diffusion is down, the concentration 
gradient. 
So the gap junctions then are allowing 
the diffusion of ions and notably calcium 
from one cell to the other cell. 
And this occurs through all the cardiac 
myocyte of the heart that are 
contractual, so these cells are all 
connected to one another. 
So that when they contract, they, they, 
have a wave of calcium that goes across 
all the cells. 
And they all contract, synchronously. 
So the characteristics, then, of the 
simple diffusion, is that it's going, the 
molecule is going to move from a high to 
a low concentration, that it requires no 
energy expenditure. 
And third, that it will continue until 
the equilibrium is reached, that is, we 
will have equal concentration of 
materials on either side of the membrane. 
Forth, it occurs rapidly over short 
distances but very, very slowly over long 
distances. 
So we can move materials from the 
vasculature across the interstitial 
space, which is pretty narrow. 
and into the cells, by diffusion. 
But it would be, it would take way to 
much time to move materials from the GI 
tract all the way to the lung or to the 
brain by diffusion. 
So we have to have the cardiovascular 
system. 
Which has a pump and moves material by 
pull, by bulk flow. 
Five, the simple diffusion is directly 
related to temperature, so if I increase 
temperature,the system will go faster. 
If I decrease temperature, the system 
slows. 
And six, it's inversely related to the 
size of the molecule. 
So if the molecule is very large, then 
it's going to be a very slow diffusion 
for that molecule. 
If the molecule is very small like an 
ion, say a sodium ion, then the diffusion 
path can be quite rapid. 
And seven, we have, the diffusion will be 
dependent on the total surface area 
that's available. 
So a large surface area, we have a lot of 
diffusion, a very small surface area, a 
very small amount of material that can 
cross at that particular point. 
Its also dependent on the thickness of 
the membrane that it's going across. 
So and this going to be very important 
when we talk about the respiratory tract 
because if there isn't if the membrane 
between, between the air space and the 
vasculature thickens because we have 
water in that area. 
Or we have some kind of fibrosis so we 
have connective tissue in that area. 
The diffusion path for gases will be, 
will be lengthened, and then the 
diffusion of the gas across that region 
will be impaired. 
And we'll talk about that some more when 
we talk about the respiratory tract. 
So that's the, the simple diffusion, and 
that works for hydrophobic molecules. 
But molecules that are not soluble in 
lipid, that is, molecules that are 
hydrophilic. 
They're polar molecules. 
They're charged molecules. 
They can not move across the plasma 
membrane by simple diffusion. 
Instead they use some of them are using 
what are called transporters and 
transporters are integral membrane 
proteins. 
So they are actually stuck into the 
center of the membranes. 
So if we look at this membrane and we 
have our bilayer of lipids and that's 
here. 
So this is our membrane. 
The bilayer of lipids has molecule 
that's, that's actually embedded within 
the bilayer. 
When they're embedded in that bilayer 
they're called integral membrane 
proteins. 
This particular integral membrane protein 
can be open to, in this case, the ECF, or 
the extracellular fluid space. 
But it can change its conformation and 
then opens to the intracellular membrane 
fluid space. 
And it goes so by simply flipping back 
and forth across the membrane, so a 
particular example of this would be the 
glut, the glut transporter, that is the 
glucose transporter or the gluts. 
This is a family of transporters that can 
move glucose into cells and all cells 
have glut transporters. 
The glucose can enter into our, our, our 
carrier, this, this transporter. 
And as it enters into the transporter 
from the extracellular fluid space, then 
there's a, there's a conformational 
switch, and now the glucose is released 
into the interior of the cell. 
This particular carrier, transporter can 
move in, in both directions, and so the 
net flux or the net flow of the material 
across the membrane is dependent upon the 
concentration of the material. 
So if the material has a high 
concentration in the ECF. 
Then we will have a net movement of the 
glucose into the cell. 
But this, the glucose that's within the 
cell can also enter into the transporter 
and move back across the membrane. 
So it is, it is a system which, which 
simply is active depending upon the 
fusion gradient. 
So this is called facilitated diffusion 
because we're using an integral membrane 
protein to move the ma-, the solute 
across the membrane. 
And there's a couple of things about the 
facilitated diffusion that we should, we 
should think about. 
One is, is that they're specific, these 
transporters are specific for, for a 
given solute. 
So the glucose transporter transports 
glucose, but it does not transport an 
amino acid or peptide or something like 
that. 
The second thing is that there's a finite 
number of these on the membrane surface 
so that we can under certain 
circumstances saturate all of these 
transporters. 
And at that point we can't get any 
further transfer of material across the 
membrane. 
That is our flux, our net flux across the 
membrane becomes constant. 
And that's what we can see here on this 
next diagram. 
So here I've diagramed then the flux 
versus the solute concentration. 
So let's say this was our glucose. 
The glucose in the ECF. 
And that the solute concentration is 
increasing as we go towards in this 
direction. 
The flux of course is our transport rate 
across the membrane itself. 
And if we look at the simple diffusion, 
the simple diffusion would be for urea 
for instance. 
then the urea as we increase the urea 
along the x-axis. 
So if we increase urea along here, the 
solute concentration of urea. 
Then the urea is moving in a linear 
fashion, and it, never as it tops. 
But if we look at the facilitated 
diffusion fort the glucose, then what we 
see is that glucose will saturate at, all 
of the receptors or all of their 
transporters at this point. 
So that at that point anything, any 
concentration of glucose beyond that does 
not cause an increase in the transfer 
rate. 
Or in the flux across the membrane. 
Now, some of these transporters are able 
to take more than one solute at a time. 
For instance, we can have a transporter 
that will move glucose and sodium 
together. 
And these occur within the 
gastrointestinal tract. 
They also occur within the renal tubules. 
This sodium glucose transporter is a 
co-transporter taking two solutes across 
the membrane at the same time. 
And again, it will load on one side of 
the membrane, undergo a conformational 
change, and then release the material on 
the other side of the membrane. 
And here again is our hydrophobic our 
hydrophobic bilayer. 
If the, if the molecules, the sodium and 
the glucose in this case, are moving in 
the same direction - they're going from 
the ECF into the ICF - then it is called 
a symporter. 
If they're moving in the same direction 
and importantly this only works if both 
the sodium is present and the glucose is 
present. 
So, we have to have both solutes present 
in order for this transporter to work. 
But, we do have in some instances 
antiporters and the antiporters are again 
we can find these in the, in the 
gastrointestinal tract and within the 
renal system within the renal tubules. 
And here, we are moving both, the sodium, 
in this case, a sodium and a proton, but 
they're moving in opposite directions. 
So, this transporter, as it's moving a 
sodium into the cell, is moving a proton 
out of the cell and into the ECF. 
Because they're going in the opposite 
directions, the is called an antiporter. 
Again, there specificity within these 
transporters, there are only are binding 
the specific solutes and both solutes 
have to be present for the transporters 
to work. 
And again, there is a finite number of 
these on the cell surfaces and therefore 
the transfer of material from one side of 
the membrane to the other can be 
saturated. 
And we do have instances where there's 
actually a pore made across the plasma 
membrane. 
So again we have our hydrophobic barrier 
which is our bilayer of lipid and these 
are integral membrane proteins which are 
inserted within the membrane but when 
they're open, there is a aqueous pore 
that goes all the way across the 
membrane. 
And example of one of these is the 
aquaporin. 
Aquaporin is a pore which is used for 
moving water across the membrane. 
In almost all cells aquaporins are 
present, so water will almost immediately 
reach equilibrium across the plasma 
membrane. 
But under some circumstances, we have 
channels where the, the pore is gated. 
That is, it's closed, and there's a 
regulated opening of the pore, and this 
regulated opening of the pore is called 
gating. 
In both cases, when the pore is open, 
then the movement of the particle across 
the channel will be by diffusion. 
And we will be moving from high 
concentration to low concentration. 
So in the case of the aquaporin, we could 
have water, which is higher in 
concentration in the ECF. 
And the water then will then move to the 
ICF. 
At a very rapid rate. 
So how, then, are these channels, gated? 
The channels can be gated by three 
different mechanisms. 
The first is a Ligand gating. 
This simply is a chemical which will bind 
to the channel itself. 
And the channel will be in, in a closed, 
position and when this ligand binds to 
the channel, it'll cause the channel to 
open. 
An example of this is the acetylcholine 
receptor. 
This is a neurotransmitter for the 
parasympathetic system, nervous system. 
This acetylcholine receptor binds to a 
nicotinic receptor on skeletal muscle. 
So this nicotinic receptor on this 
skeletal muscle is a channel. 
It is a sodium channel. 
And when the acetylcholine binds to the 
channel, the channel opens and sodium can 
enter into the cells. 
It enters into the skeletal muscles. 
And we'll talk about the, what happens 
after the sodium enters into the skeletal 
muscle when we deal with skeletal muscle. 
This channel will only allow sodium to 
cross and the channel will only open when 
there is acetylcholine present and that 
can bind to the receptor itself. 
In the second type of channel, these 
channels are opening to voltage. 
And when we've not really talked about 
how there is a charge difference, a 
charge gradient, across the plasma 
membranes. 
We've said that there's a chemical 
gradient across the plasma membranes, so 
that sodium is high on the outside of the 
cell and very small on the inside, a 
small concentration on the inside. 
Potassium is very high on the inside of 
the cells and has a very small 
concentration on the outside of the 
cells. 
So that's a chemical gradient across the 
plasma membranes of all cells. 
But there is in fact a, a voltage 
gradient. 
That is a charge gradient across the 
membranes as well. 
And this charge gradient is due in part 
to the negatively charged proteins that 
are inside cells. 
So the inside of a cell is more negative 
than the outside. 
So the ECF is a, is more positive 
relative to the inside of the cell. 
When, when the voltage that is the charge 
across this membrane changes, and it can 
change in certain cell types such as, 
neurons or muscle, then if the, it 
reaches a specific difference across a 
difference in voltage, across the 
membrane it can open channels. 
And one of the channels that, that will 
open is a voltage gated calcium channel. 
The voltage gated calcium channels are 
present in muscle, in cardiac muscle. 
And then, at a certain, at a certain 
voltage, at a certain change in voltage 
across the membrane, these channels will 
open, and then at a certain voltage these 
channels will again close. 
And we'll talk about these some more when 
we talk about the cardiovacscular system 
and the heart. 
And the last kinds of gating we see is 
mechanical gating. 
Mechanical gating is found in smooth 
muscle. 
So in smooth muscle, we have a situation 
where the smooth muscle has, around the 
artery, may have a tone, a tonic 
contraction which is a basal contractual 
state. 
If more blood vessel, more blood is 
delivered to that vessel then the walls 
are stretched. 
And when the walls are stretched you open 
these mechanically gated channels calcium 
can enter and the calcium causes the 
smooth muscles to contract and the cells 
will go back to their original contracted 
state. 
So that the vessel diameter then will go 
back to its original basal state. 
And again, we'll talk about this more 
when we talk about the cardiovascular 
system. 
So those are our channels. 
So, with the transporters and the 
channels, then, the movement of materials 
across the membrane once the, once the 
opening is, is present, then the movement 
is going to be by diffusion. 
But with pumps, we are moving materials 
not from a high to a low concentration 
but in the opposite direction and that's 
what shown here. 
So with pumps we're going to have an a 
high concentration of material on one 
side of the membrane. 
And let's say that's calcium and this is 
in the ECF so these little green dots are 
calcium and then in the intracellular 
space we have calcium and it's a very 
small amount of calcium. 
Our, our, pumps are enzymes, the, and 
they're enzymes which will cleave usually 
ATP. 
So they cleave and, they cleave an ATP 
molecule, which is an energy molecule 
within the cell. 
By cleaving ATP, they will undergo a 
different conformation, and that allows 
the molecule to, to cross the membrane. 
And that's what's shown here. 
So we bind ATP to an inactive pump. 
The calcium ATPAse and we bind calcium to 
the calcium ATPAse on the inside of the 
cell. 
It undergoes a conformational change, and 
when it does so the calcium is extruded 
to the extracellular space. 
So we're moving calcium then from a low 
concentration to a high concentration. 
Exactly the opposite of what we saw with 
simple diffusion and facilitated 
diffusion and this requires energy. 
There are many really important pumps 
within the cells of the body. 
One of course we've already talked about 
is the sodium potassium ATPAse. 
This is the pump that maintains the 
volume of all cells. 
And it allows us to keep a steady state 
of sodium and potassium across the plasma 
membranes. 
We also have the calcium ATPAse, which we 
just talked about, and these are present 
in muscle cells. 
So, they're, we're going to move calcium 
across membranes. 
Removing calcium quickly from the inside 
of a cardiac myocyte, for instance, in 
order to be able to relax the cell and to 
then be ready for the next contraction. 
We also use these pumps in other areas 
such as the stomach where we make acid. 
So in order to make acid you extrude a 
proton into the lumen of the stomach, and 
you do so by using a proton potassium 
ATPase. 
And we'll talk about that when we talk in 
the, about the stomach in the GI tract. 
So, this one last concept that we need to 
talk about, and this is a little 
difficult for students to understand 
sometimes. 
There are areas of the body where we 
want to move materials all the way across 
a cell, not just going into the cell, but 
across the cell, and into the blood 
stream. 
And we're starting with the lumen such as 
the gastrointestinal track. 
You just ate your Big Mac, and we now 
have glucose sitting in the lumen of the 
gastrointestinal track, and we want to 
move it across the epithelium into the 
blood on the other side and then 
delivered that to the, to the liver and 
to the cells to the body. 
And we do that not with by a primary 
active transport which we just talked 
about, which is a simple pump moving it 
across. 
But that we use two different entities 
and we, the two entities are working in 
coordination. 
So this is called a secondary active 
transport. 
So, the secondary active transport 
requires a ATPase pump on one surface of 
the cell. 
And usually, on the basal surface of the 
cell. 
That's the s-, the side that's facing the 
bloodstream. 
And then on the lumen or the apical 
surface of the cell. 
We have a co-transporter, and that's 
what's shown here. 
So this happens to be the sodium glucose 
co-transporter that we talked about 
already, and in the, in the 
gastrointestinal tract, it's known as the 
SGLT, or the Salt Glucose Transporter. 
Both glucose and sodium will bind to this 
transporter. 
It's a co-transporter and it's a 
symporter. 
So the both the sodium and the glucose 
enter into the cells. 
And when they enter into the cells, the 
glucose then is at the high 
concentration, and it will diffuse across 
the cell and leave the cell at the, at 
the luke basal surface, through a simple 
transporter, which is a by facilitated 
transport for glucose. 
So, this is just simply our glut 
transporter. 
So, glucose then exits the cell and 
enters into the blood. 
And sodium, on the other hand, is, moves 
across the cell, and then the sodium is 
pumped out of the cell actively by the 
sodium potassium ATPase . 
Which moves three sodiums out for every 
two potassiums that enter. 
And this pump requires an ATP, so it's an 
enzyme which cleaves ATP, so that the 
energy is moving the sodium from the 
interior of the cell to the outside. 
And we know that's moving the sodium 
against its concentration gradient. 
The glucose, in a sense, gets a free 
ride. 
The glucose is using the sodium gradient 
and the sodium gradient is maintained by 
the sodium potassium ATPase, which is at 
the opposite side of the cell. 
So we have a, a transporter, a 
co-transporter, which is linked to a 
active transport of one of the solutes, 
and that sets up the gradient where the 
other solute then is able to just, to 
just essentially piggy back or or get a 
free ride as it goes across the cells. 
And we'll talk about this trans cellular, 
transport in much more detail when we 
talk about the gastrointestinal track and 
in the renal tubules. 
Okay, so one of our general concepts. 
So the first is that the movement of a 
solute across the lipid bilayer, the cell 
membranes, is dependent on its size, its 
charge, and its solubility. 
The second is that the net flux, or 
movement of the solute will be determined 
by it's gradient. 
Third that permeable solute crosses the 
membrane by simple diffusion. 
And this is a slow type of a movement 
across the membrane, and it is a more 
general type of movement. 
So it's anything that soluble and lipid 
can move across this. 
So this would be some of the steroid 
hormones, it could be urea. 
These are pro-, these are molecules which 
are able to cross the membranes without 
having a specific transport. 
And they will always move down their 
concentration gradient. 
And they will move down the concentration 
gradient until they reach an equilibrium, 
so that you will have an equal 
distribution of materials on either side 
of the membrane. 
Fourth, we have non-permeable solutes 
will cross the membrane by facilitated 
diffusion. 
This is going to be fast. 
It uses transporters. 
These are those integral membrane 
proteins. 
And the process, again, requires a 
gradient, is saturable, and is specific. 
And that’s because it’s using a 
transporter. 
So this is a much more, targeted type of 
movement of materials across the 
membranes and into the cells. 
Five, primary active transports moves a 
solute against its concentration 
gradient. 
And this mechanism requires ATP. 
So we have to cleave ATP in order to be 
able to move this material across the 
membrane. 
Again, it will show specificity. 
The sodium potassium ATPase moves sodium 
and potassium in an, in an anti in an 
anti manner. 
But that it will move protons out of the 
cells, if it's a proton ATPase. 
But if it's a proton ATPase it will not 
be moving sodium and potassium across the 
membrane. 
And again, these things will be 
saturable, we'll have a finite number of 
these pumps that are going to be on the 
plasma membrane surfaces. 
And six, secondary active transport 
couples the activity of a co-transporter 
with a pump. 
So, under this condition, we will then 
have we will, we will then have the 
active extrusion of one of the solutes, 
that's coming in with that, with that 
co-transporter. 
And this is the mechanism that's used for 
transcellular transports of solutes 
across the gastrointestinal track 
epithelium and across the renal tubules 
epithelium. 
So we're moving from a luminal surface 
all the way across the epithelium to get 
into the blood space. 
Okay, so the next time we come in here 
then, we're going to consider how we move 
water across the plasma membranes, so see 
you then. 

